A study on the incidence of Candida albicans was carried out on pregnant and non-pregnant women at the Federal Medical Centre and general Hospital Owerri. High vaginal swabs were used for the study. A total of 120 women were examined for Candidaalbicans; of which a total of 80 were pregnant women and the remaining 40 were non-pregnant women (used as control). The microbiological standard of identification of the organism was adopted. Of the 80 pregnant women examined for Candidaalbicans, 68 were infected, which represents an incidence of 85.0%. Of the 40 non pregnant women (control) examined, 16 were infected, which represents an incidence rate of 40.0%. Greatest percentage of 58.8% and 56.2% were recorded in the age group of 18-28 respectively. The pregnant women had a higher incidence rate of 85.0%. The clinical symptoms noted amongst them were itching, irritation of the vulva and a white, cottage cheese-like vaginal discharge.

CHAPTER ONE

INTRODUCTION

Candida are small, oval yeast measuring 2-4 mm in diameter. It causes a disease condition known as candidiasis. Candidiasis is considered an opportunistic and a sexually transmitted infection. It constitutes great health problems to many women. More so, there has been rampant complaints of pregnant and non-pregnant women who attend clinics at Federal Medical centre and general Hospital Owerri about vagina itching and discharge. Being that this is a common symptom of candidiasis, it has become expedient to establish the incidence of this microorganism amongst the population of these women.

In the history of medicine and scientific exploration, new discoveries are made on a regular basis; in fact, many people devote their lives to the identification and treatment of disease. When these disease are discovered, it is often assumed that they are new. These diseases might well have been with us for many years (Marshall et al: 1983).

Although, the term infection and diseases are sometimes used interchangeably, they differ somewhat in meaning. Infection is the invasion or colonization of the body by pathogenic microorganisms, while disease occurs when an infection results in any change from a state of health.

Disease is an abnormal state in which part or all of the body is not properly adjusted or is not capable of carrying on its normal function.

An infection may exist in the absence of detectable disease. Once a relationship between the normal micro biota can benefit the host by preventing the overgrowth of harmful microorganisms; a phenomenon called antagonism (Tortora et al; 1995).

Microbial antagonism involves competition among microbes; one consequence of this competition is the host against colonization by potentially pathogenic microbes by competing for nutrients, producing substances harmful to the invading microbes, and affecting conditions such as PH and available oxygen. When this balance between the normal microbiota and pathogenic microbes is upset, disease can result. For example, the normal bacterial microbiota of the adult human vagina maintains a local PH of 3.5 to 4.5(Marshall et al; 1983). The presence of the normal microbiota inhabits overgrowth of the yeast Candidaalbicans, which cannot grow under these conditions and is normally present in small numbers in the vagina. If antibiotics, excessive douching or deodorants eliminate the bacteria population, the PH of the vagina reverts to nearly neutral and Candidaalbicans can flourish and become the dominant microorganism there.

Candidasis is a disease caused by yeast-like fungus, Candida albicans; that often grow on mucous membranes of the mouth, intestinal tract, and genito-urinary tract. Infections are usually a result of opportunistic overgrowth when antibiotics or other factors suppress the competing microbiota. It is responsible for occasional cases in non-gonococcal urethritis in male and for vulvovginal candidiasis which is the most common cause of vaginitis. About 75% of all women experience at least one episode.

The lessons of Vulvovaginal candidiasis resemble those of oral thrush but produce more irritation, severe itching, thick yellow cottage, cheese-like discharge, and a yeasty odour. Candidaalbicans is an opportunistic pathogen. Predisposing conditions include use of oral contraceptives and pregnancy, Which causes an increase in glycogen in the vagina. Diabetes, and treatment with broad-spectrum antibiotics are also associated with the occurrence of candida albicans and vaginitis, (Tortora et al; 1995).

Candida albicans and its close relatives account for nearly 80% of nosocomial fungi infections in general (Talaro, 2008).

The Federal Medical Centre and general Hospital Owerri have both ante-natal and out-patient units; where they render different services to patients. Therefore provide a fertile ground for an investigation such as this

Candida albicans is opportunistic dimorphic pathogenic yeast which is present on the human mucosal epithelial cell surface (willey et al, 2008). It causes the majority of opportunistic fungal infection. Candidiasis is the mycosis caused by Candida albicans or other Candida species, (Braga et al, 1996). It adhesion is considered therefore to be an important first step in the pathogenesis of symptomatic or asymptomatic infections of buccal or vaginal mucosa, (Dupont, 1996).

In contrast to the other pathogenic fungi, candidaalbicans is a member of the normal microbiota within the gastrointestinal tract, respiratory tract, vaginal area and mouth. In healthy individuals they do not produce disease because growth is suppressed by other microbiota and other host resistance mechanisms.

However, if anything upsets the normal microbiota and immuno competency, Candida may multiply rapidly and produce, Candidiasis. In some hospitals they may represent almost 10% of nocosomial bloodstream infections. Because Candida can be transmitted sexually, it is also listed by the centre for disease control, 2004 as a sexually transmitted disease, (Talaro, 2008).

No other mycotic pathogen produces as diverse a spectrum of disease in humans as does Candida (Talaro, 2008). Most infections involve the skin or mucous membranes. This occurs because Candida in a strict aerobe and finds such surfaces very suitable for growth. Cutaneous involvement usually occurs when the skin becomes overtly moist or damaged.

Oral Candidiasis, or mouth thrush, is a common disease in newborns. It appears as many small, white flecks that cover the tongue and mouth. At birth newborns do not have a normal flora in the oropharyngeal area. If the mother’s vaginal area is heavily colonized with Candida, the upper respiratory tract of the newborn becomes colonized during passage through the birth canal. Thrush occurs because growth of Candida cannot be inhibited by the other microbiota, thrush becomes uncommon (willey et al, 2008).

Vulvovaginal Candidiasis known more commonly as yeast infection, has widespread occurrence in adult women as a result of complication of diabetes, antibiotic therapy, oral contraceptives, pregnancy or any other factor that can disrupt the normal vaginal flora.

The chief symptoms of vaginal candidiasis (V C) are a yellow to white, cottage cheese-like discharge, inflammation, painful ulcerations, itching, soreness and irritation in the vulva (the vulva refers to the external genital organs of the female). The most severe cases spread from the vagina and vulva to the perineum and thighs.

Candidalbalanitis (inflammation of the head of the penis) can develop in the male partners of women with thrush; however, it is very rare; male genital yeast infection is much less common than female genital yeast infection.

Of all the areas of the gastrointestinal tract, Candida most often infects the esophagus and the anus. Esophageal candidiasis, which afflicts 70% of AIDS patients, causes painful, bleeding ulcerations, nausea, and vomiting. (Talaro, 2008).

Candidal attack of keratinized structures such as skin, hair and nails, called onychomycosis, is often brought on by predisposing occupational and anatomical factors. People whose occupations require their hands or feet to be constantly immersed in water are at risk of finger and nail invasion. Intertriginous Candidiasis occurs in most areas of the body where skin rubs against skin, as beneath the breasts, in the armpit, and between folds of the groin. Cutaneous candidiasis can also complicate burns and produce a scald like rash on the skin of neonates whose diapers are not changed frequently and therefore are not kept dry (Talaro, 2008).

Candidal blood infection usually becomes systemic in patients chronically weakened by surgery, bone marrow transplants, advanced cancer, and intravenous drug addiction. The presence of candida albicans in the blood is such a serious assault that it causes more human mortality than any other fungal pathogen. Principal targets of systemic infections are the urinary tract, endocardium, and brain. Patients with valvular disease of the heart are vulnerable to Candidal endocarditis, usually caused by other species (Candidatropicalis and Candidaparapsilosis). A recent development is the tendency of this fungus to produce biofilms on artificial joints, catheters and heart valves. In most of these cases, the colonization is very drug resistant and may require removal of the device until it can be controlled. Candida has reportedly cause terminal infections in bone marrow transplant patient and in recipient of anticancer therapy (Talaro, 2008).

A presumptive diagnosis of Candida albicans in a vaginal smear (stained) reveals Gram positive budding yeast cells attached to a pseudohyphae, and true hyphae. In many case of vaginal candidasis, infection is detected during a routine pap smear specimens are cultured on standard fungal media incubated at 300C. Identification is complicated by the numerous species of Candida and other look-alike yeasts. Growth on a selective, differential medium containing trypan blue can easily differentiate Candida species from the yeast Cryptococcus. Colonies of Candida albicans appear pale blue on trypan medium, whereas Cryptococcus is dark blue. Confirmation evidence of Candidaalbicans can also be obtained by the germ tube test, the presence of chlamydospores, and multiplepanel systems that test for biochemical characteristics. A sensitive DNA amplification technique has been developed for identifying this species directly from clinical specimens (Talaro, 2008).

Another characteristic of Candida albicans is the production of curved, elongated germ tubes within three hours when the yeast is transferred from a peptone containing medium to mammalian serum at 370C. Growth requirements are simple, on sabouraud’s medium, colonies usually reach 0.5mm in diameter after 18hours and develop into high convex, off white colonies 1.5mm in diameter after two days. The behaviour of Candida albicans on other media, its failures to split urea can be used in differentiating it from other yeast (Torulopsis, Cryptococcus) and from other candida species. Candida is tolerant of acid and not sensitive to any antibacterial drug; it thrives in its normal sites in the body when broad spectrum antibiotics restrain the growth. It uniformly sensitive to the polyene antibiotics and clotrimazole and usually sensitive to 5-fluorcytosine. (willey et al, 2008).

Microscopically, according to Talaro (2008), Candidaalbicans has a budding cells of varying size that form both elongated pseudohyphae, and true hyphae. Macroscopically, it forms a white to cream coloured paste with a yeast odour.

Candida albicans is the commonest cause of candidiasis. The yeast’s commensal relationship with humans enables it when environmental conditions are favourable, to multiply and replace much of the normal flora (Braga et al, 1996). Candida can be detected in unstained wet preparation of the skin, urine, vaginal discharge or other exudates from mucosal surfaces (Cheesbrough, 2000).

Candida albicans occur as a normal flora in the oral cavity, genitalia, large intestines and skins of 20% of humans (Talaro, 2008). Without candida in the intestine, we would be defenseless against many pathogenic bacteria (women’s health, 2005). The yeast state of the dimorphic candida is a non-invasive, sugar fermenting organism while in its fungal state; it is invasive and can produce rhizoids which are very long root-like structures which cause infections (women’s Health, 2005).

Some doctors have diagnosed wrongly that a patient has neurotic anxiety syndrome when they complain of depression, anxiety, recurring irritability, heart burns, indigestion, lethargy, extreme food and environmental allergies and other infection or situations that have not been associated with any disease conditions (Molero et al, 1998). It has been established that most patients that come up with these complaints are actually infected by Candidaalbicans (Molero et al 1998).

Candida species are more than 100 that exist in nature, only few species are recognized as causing diseases in humans. Medically significant Candida species include the following, Candida glabrata, Candida kruseri, Candida dubliniesis, Candida albicans (Hidalgo, 2005). As Candida proliferates in the intestine, it can change its anatomy and physiology from the intestine, it can change its anatomy and physiology from the yeast-like form to the mycelia form (Dimorphic character). The fungal rhizoids can penetrate mucosa or intestinal walls, leaving microscopic holes and thus, allowing toxins, undigested food particles, bacteria and yeast to enter the blood stream which is known as “leak gut syndrome” (Roth, 2005). Penetration of the gastrointestinal mucosa can break down the boundary between the intestinal tract and the rest of the circulation and allow entrance into the blood stream of many antigenic substances. Usually candidaalbicans can cause bronchial or pulmonary disease only in patients already debilitated or rendered susceptible by other diseases.

The presence of this organism in tropical sprue is only of secondary importance; but the prominence of oral and upper respiratory tract as well as the urinogenital tract colonization especially in females; gave considerable impetus to medical mycology during its infancy, which have developed an appropriate experimental animal models to analyze the virulence of particular mutants which may help understand the molecular basis of Candida albicans (Cassone and korting, 1999).

The ubiquity, adaptability and pathogenecity of candidaalbicans and related species during the era of antibacterial antibiotics keep these fungi constantly before the medical mycologist as important primary cause of a few forms of candidiasis. Candidiasis, also known as a yeast infection is a common fungal infection that occurs when there is a overgrowth of the Candida fungus (Ryan, 1996).

There is some evidence that HIV may also play a direct role in candidiasis and thus research has linked oral candidiasis (thrush) in HIV-infected people to high viral load, regardless of CD4 counts (Aidsmap, 2004).

Authors with this perspective showed that Candida was a normal inhabitant of the vagina and that pregnancy leads to thrush in women. Pregnant women are more often affected than their non-pregnant counter parts; though large numbers of otherwise healthy women of childbearing age (15-25 years) are more prone to this infection because of their sexual activeness and the likelihood of recurrent pregnancies (fidel et al;1995).

However, oral thrush does not develop in women until the fourth to fifth day of life, and thrush may develop in older children and adults who are suffering from multiple endocrine disturbances, underlying deficiencies in natural defense mechanisms. It may also be seen as a complication of diabetes or of therapy with immuno-suppressive antibiotics, or in cancer. Poor oral hygiene or trauma may also facilitate establishment of Candida albicans.

Another frequent involvement of Candidaalbicans is in infection of the mucosa of the vagina, called vaginal candidiasis or vaginitis. Vaginitis is characterized by excessive discharge with a characteristic clumpy, white cottage-cheese appearance. Approximately three quarters of all women suffer at least one attack of Candida vaginitis or the other (Botu, 2002). There are a number of predisposing causes of vaginal Candidiasis, they include pregnancy, use of oral contraceptives, diabetes, immune defects-both natural and induced, clothing, personal habits and antibiotics therapy.

Unlike vaginitis, Balanitis or Candida balanoposthitis is not common and usually contracted by man from his female partner. Balanitis manifest with an acute inflammatory reaction which resembles the vulvitis seen in women. However, more commonly, 15% or 20% of male partners develop an acute hypersensitivity reaction (Sobel, 1996).

Cutaneous involvement of Candidaalbicans may also occur, in case of poorly maintained hygiene, and moist skin which may provide favorable conditions for establishment and proliferation of Candida albicans with the development of paronychia, onychomycosis, and diaper rashes. The cell wall of candida aldicans is not only the structure in which many biological functions essential for the fungus cells reside but is also a significant source of Candida antigens (Martinez et al, 1998). Proteins and glycoprotein’s exposed at the external layers of the cell wall surface are involved in several interaction of fungal cells with host antibiotics; has the potential to influence profoundly the host-parasites interactions by affecting the antibody-mediated functions such as opsonin-enhance phagocytosis and blocking the binding actively of fungal adhesions for ligands (Martinez et al, 1998).

PATHOGENESIS

As already stated above, mycology is the study of fungi. Approximately 80000 species of fungi have been described, but fewer than 400 are medically important, and less than 50 species cause more than 90% of the fungal infections of humans and other animals (Sobel, 1996).

Fungal infections are mycoses. Most pathogenic fungi are exogenous, their natural habitats being water, soil and organic debris. The mycoses with the highest incidence-candidiasis and dermatophytosis are caused by fungi that are part of the normal microflora or highly adapted for survival on the human host.

Candida albicans is the most important pathogenic species of candida and is usually the etiologic agent of oral vaginal thrush (Molero et al 1998).

Contrary to the general rule in mycology, fermentation reactions are useful in the recognition and differentiation of species of Candida. Castellanis, in his early studies established the usefulness of the procedure, but refinements in the precision of the list have altered some his standards for specific identification (Molero et al, 1998).

The microbiological presence of Candida albicans does not necessarily equate with disease. Depending on the age group, geographic location and socio-economic status, up to 44% of women may habour one or more species of Candida as a normal constituent of vaginal flora, (Boyer and Kienik 2000).

Although, candidiasis of the female genital tract is a monoetiologic disease, the pathways which is possible for any normal genitalanal microflora to attain pathogenic expression are enough for classification, especially for the selection of appropriate treatment (Monif, 2003).

PREDISPOSING FACTORS THAT AFFECT GROWTH OF CANDIDA ALBICANS.

Factor 1-Primary Candidiasis

Factor 11- Antibiotic Induced Candidiasis

Resulting from systemic therapy for now vulvovaginal infection

Resulting from local or systemic therapy for vaginal infection (ping-pong vaginitis) and

Almost all antibiotics are responsible for Candidiasis and especially, the broad spectrum antibiotic such as tetracycline, ampicillin, and cephalosporins. It was observed that after 2-3 weeks of treatment with tetracycline even at low dosage; vaginal carriage increased from about 10%-30% and accompanied by simultaneous increase in isolation of Candida from the gastrointestinal tract (Oriel, 2001). Studies of the gastric flora of rats revealed that lactobacilli and candidaalbicansexists in harmony; cach colonizing anatomically distinct areas (shabba, 1983). Lactobacilli occupy the keratinized stratified sequence epithelia and are attached to the secretary mucosal cells. After antibiotic therapy; lactobacilli are usually eliminated and candida multiply and colonize the entire mucosal surface (Shabba, 1983). Whereas pin-pong vaginitis is a variant antibiotic induced Candidiasis; after the therapy for antecedent genital tract infections.

III

One of the most common factors which is recognized as predisposing cause of vulvovaginitis is pregnancy, during which vaginal yeast carriage is more frequently and continues to increase with the duration of the gestation (Morton and Rashid, 1997). The mechanism by which pregnancy encourages colonization are complex.

Most authors attributed this to increased vaginal epithelia and glycogen content under the stimulation of reproductive hormone. (Oriel, 2001).

Certain glycogen (carbon source) enhances yeast growth multiplication, adherence, and germination; but the recent identification of receptors in the cytosol of candida for estrogens and progesterone together with the observed stimulatory effect of these hormones points to the direct virulence-enhancing effect of female reproductive hormones. (Power, 2001). The effect is not only on yeast but also on the receptor sites and adherence of the individual vaginal epithelial cells. (Sobel, 1996).

Several authors observed that vaginitis developed in about 10% of pregnant women during the first trimester (Hurley and jawetz, 2006).

Additionally, use of oral contraceptives increase colonization rate from 20%-45%.

Uncontrolled diabetes mellitus studies on Candida infections of the vagina, accompanying glucosuria and increased glucose concentration in the vaginal secretions may precipitate vulvovaginitis, since availability of sugar influences the adherence and growth of candida.

Sex hormones from certain experiment made by some scientists are being used to evaluate the systemic use of corticosteroids in Candidiasis and discovered to their surprise that these hormones predispose to infection, which invariably leads to vaginal discomfort with swelling, dryness and itching, after about 12-72 hours post inoculation. Thus, human vaginal candidiasis proved to be more persistent and longer lasting during gestation; this as already stated above is attributed to hormonal changes and other factors of the organism (fidel et al, 1995).

HOST DEFENCE MECHANISM

GENITAL TRACT ANTIBODIES

Little is known about the natural vaginal mechanisms that resist candida colonization and symptomatic infection. However both serum and local cervical antibodies to candida albicans have been identified in both symptomatic and asymptomatic vulvovaginal candidiasis (Martinez et al 1998).

The dominant anticandidal immunoglobulin in cervical secretion is IgA, especially the secretary type. (Waldman, 1997) studied immunoglobulin levels in vaginal secretions and find that 1gA predominated but 1gG levels were high in many cases, and Millne, found IgG antibodies to Candidaalbicans in vaginal secretion of around 22% of women examined and 1gA antibodies in around 7%, there was little difference in frequency of antibodies between women with vaginal candidiasis, symptomless carriers and those with no yeast present (Martinez et al, 1998).

CELL MEDIATED IMMUNITY

The role of cell mediated immunity in preventing vaginal colonization is unclear. It was observed that almost all adults have a normal Cutaneous delayed hypersensitivity reaction to the introduction of Candida antigen. Similarly, in vitro lymphocytes studies show normal proliferation responses of lymphocytes to mitogens (Itah, 2006).

Additionally, Iymphocytes or serum from chronic vaginitis patients suppressed the proliferation responses of control Iymphocytes to candida albicans but not to mitogens.

THERAPY OF CANDIDIASIS

Although candidiasis and fungal infections in general range form a completely subclinical illness to progressive and fatal disease, the great majority of infected patients who come to physicians or who are encountered in the hospital still present a challenge to the gynecologist. Prominent among their presenting symptoms are such typical manifestation as weight loss, itching, painfulness etc.

Since candidiasis are acquired either through the respiratory route or through the urinogenital tract of females, special (medical) attention are placed on these areas.

CHEMOTHERAPY AND TREATMENT OF CANDIDIASIS

Candidasis, which is opportunistic; will return in many cases if the infection is not well treated. Therapy for superficial mucocutaneous infection consists of tropical antifungal agent (Azoles and polyenes). A new class of antifungal drugs, terbinafine, has been approved for treating Onychomycosis. Amphotericin B with or without flucytosine and fluconazole are usually effective in system infections. Recurrent bouts of Vulvovaginits are managed by topical azole drugs ointment now available as over-the counter drugs. Vaginal Candidiasis is sexually transmitable, thus it is very important to treat both sex partners to avoid reinfection Vagina (Talaro, 2008).

It is therefore important before treating a Candida infection to try to identify the underlying circumstances that have allowed it to establish itself. If the underlying disturbance such as poor hygiene or diabetes can be corrected, the body will usually deal with yeast. Treatment will however shorten the process. When the underling condition cannot be altered quickly as in pregnancy debility or serious disease, the usual treatment is to give the polyene, nystatin locally. Nystatin is very poorly absorbed form the gut so that systemic infections must be treated with Amphotericin B, another polyene (which has to be given intravenously) with 5-fluorocyrosine or with clotrimazole. Superficial infections can also be treated with other polyenes and one of them, trichomycin, is often used in vaginitis as well as against Candida. However, if this is done to avoid making an aetiological diagnosis, the underlying reasons for the infection will not be clear and appropriate further action to prevent recurrence cannot be prevented. (Tortora et al, 1995).

In addition, a wide variant of drugs are available for cure of vaginal thrush in pregnant women.

IMIDAZOLES

Clotrimazole and Miconazole as already stated are new Benzimodazoles product in the Laboratories of Bayer in Germany and Janssen in Belgium. They are relatively organic solvents as chloroform or polyethylene glycol.

Antifungal drugs which are taken or applied directly to the affected area or used vaginally are the drugs of choice for vaginal yeast infection. (CDC, 2004). Over-the –counter treatment are available; and as result, women can diagnose themselves wih volvovaginitis and treat using azoles (CDC, 2004), Drugs for candidiasis has been approved in Europe and the United state; the have good potency and low side effects (CDC, 2004); and in cases where there has been proofs and reports of fluconazole resistant candidiasis, higher doses of flconazole has been used (Drathorn, 2002). Tea tree oil is a herbal remedy that may be effective against various fungal infections of Candida although some doctors dipute its benefits.

A new class of antifungal agents is the glucan synthesis inhibitors, which block fungal cell wall synthesis (Aidsmap, 2004).

Another approach to the treatment of “difficult” yeast infection include the prevention of the conversion of the yeast form of Candidaalbicans to the fungal form since fungal form is more troublesome than the yeast form, (Aidsmap, 2004). Once the organism is arrested in its growth; and has been converted back to the yeast form, a programme is instituted to facilitate the healing of the mucosa; and it includes high level of zinc, vitamin A, Vitamin E, Vitamin B5, calcium panthothante (Molero et al 1998).

Candida infection can also be treated with topical administration of antifungal drugs such as clotrimazole (Femizole-7, Milonazle (monistale-derm, monistate vaginal) nystain triunzole (vagistate vaginal) or oral administration of flouconarde (diflucan) and Amphotericin B and more serious infection may need intravenous medication given at the hospital (Health Encylopedia, 2001).

Endogenous infections can be prevented less likely by good medical practice and avoiding injurious use of antibacterial and immunosuppressive and cytotoxic agents. Cross-infection in nurseries can be controlled and prevented by the general measures that apply to infections transmitted by contact, or infected dust (duguid et al, 1987).

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